Speaker
Description
Glioblastoma (GBM) is the most common and lethal brain cancer. It has a dismal prognosis with a 5-year survival rate of 6.8% \cite{stankovic2021vitro}. It remains one of the most challenging malignancies due to its high intratumoral heterogeneity and the ability of cancer cells to adapt to harsh microenvironmental conditions. This adaptive response is primarily driven by hypoxia, which triggers a metabolic and behavioral shift that enables cells to transition towards more aggressive stem-like phenotypes, increasing GBM resilience \cite{uribe2022adapt}. Phenotypic plasticity is also a key driver of treatment failure, fostering resistance to current therapies such as radiotherapy and chemotherapy with temozolomide \cte{amirmahani2025epigenetic}.
In this work, we present a continuum modeling framework designed to simulate the phenotypic plasticity and adaptation of GBM cells in response to hypoxia and therapeutic pressure. The proposed model describes cellular evolution through a set of internal variables that represent the phenotypic state of the cell population as a function of microenvironmental cues \cite{perez2023modelling}.
The framework was validated using both in vitro and in vivo longitudinal datasets that capture the dynamic evolution of glioblastoma under different oxygen \cite{perez2023modelling} and treatment conditions \cite{perez2024modelling}, demonstrating the model’s ability to provide not only predictions of tumor progression but also a mechanistic explainability of the underlying phenotypic shifts.
Bibliography
@article{stankovic2021vitro,
title={In vitro biomimetic models for glioblastoma-a promising tool for drug response studies},
author={Stankovi{\'c}, Tijana and Ran{\dj}elovi{\'c}, Teodora and Dragoj, Miodrag and Buri{\'c}, Sonja Stojkovi{\'c} and Fern{\'a}ndez, Luis and Ochoa, Ignacio and P{\'e}rez-Garc{\'\i}a, Victor M and Pe{\v{s}}i{\'c}, Milica},
journal={Drug Resistance Updates},
volume={55},
pages={100753},
year={2021},
publisher={Elsevier}}
@article{uribe2022adapt,
title={Adapt to persist: Glioblastoma microenvironment and epigenetic regulation on cell plasticity},
author={Uribe, Daniel and Niechi, Ignacio and Rackov, Gorjana and Erices, Jos{\'e} I and San Mart{\'\i}n, Rody and Quezada, Claudia},
journal={Biology},
volume={11},
number={2},
pages={313},
year={2022},
publisher={MDPI}}
@article{amirmahani2025epigenetic,
title={Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications},
author={Amirmahani, Farzaneh and Kumar, Saurav and Muthukrishnan, Sree Deepthi},
journal={Frontiers in Epigenetics and Epigenomics},
volume={3},
pages={1519449},
year={2025},
publisher={Frontiers Media SA}}
@article{perez2023modelling,
title={Modelling cell adaptation using internal variables: Accounting for cell plasticity in continuum mathematical biology},
author={P{\'e}rez-Aliacar, Marina and Ayensa-Jim{\'e}nez, Jacobo and Doblar{\'e}, Manuel},
journal={Computers in Biology and Medicine},
volume={164},
pages={107291},
year={2023},
publisher={Elsevier}}
@article{perez2024modelling,
title={Modelling glioblastoma resistance to temozolomide. A mathematical model to simulate cellular adaptation in vitro},
author={P{\'e}rez-Aliacar, Marina and Ayensa-Jim{\'e}nez, Jacobo and Ran{\dj}elovi{\'c}, Teodora and Ochoa, Ignacio and Doblar{\'e}, Manuel},
journal={Computers in Biology and Medicine},
volume={180},
pages={108866},
year={2024},
publisher={Elsevier}}
